Digital Commons Network^™

Homologous Recombination Deficiency Should Be Tested For In Patients With Advanced Stage High-Grade Serous Ovarian Cancer Aged 70 Years And Over, Omali Pitiyarachchi, Peter J. Ansell, Robert L. Coleman, Minh H. Dinh, Laura Holman, Charles A. Leath, Theresa Werner, Paul Disilvestro, Mark Morgan, William Tew, Christine Lee, Mary Cunningham, Meredith Newton, Babak Edraki, Peter Lim, Joyce Barlin, Nicola M. Spirtos, Krishnansu S. Tewari, Mitchell I. Edelson, Thomas Reid, Jay Carlson, Michael Friedlander

Abington Jefferson Health Papers

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group.

METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed).

RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). …

Socioeconomic Factors Influencing Hematological Health In Latin America, Lina M. Barrios, Ms

Student Papers, Posters & Projects

Hematological malignancies, also known as blood cancers, such as leukemia, lymphomas, and myelomas, are a significant health concern globally. The incidence of these malignancies has dramatically increased over time, leukemias being the leading cause. The incidence of blood cancers in Latin America exhibits regional variability, with leukemia being the emerging cause as the most prevalent type in children and young adults. However, the overall incidences are oddly lower than in developed countries, potentially due to the underreporting of the cases and the lack of cancer registries. This situation implies a critical need for improving surveillance and data collection methods to …

T-Cell Redirecting Bispecific Antibodies: A Review Of A Novel Class Of Immuno-Oncology For Advanced Prostate Cancer, Julia Palecki, Amman Bhasin, Andrew Bernstein, Patrick Mille, William Tester, William Kelly, Kevin Zarrabi

Kimmel Cancer Center Faculty Papers

Novel T-cell immunotherapies such as bispecific T-cell engagers (BiTEs) are emerging as promising therapeutic strategies for prostate cancer. BiTEs are engineered bispecific antibodies containing two distinct binding domains that allow for concurrent binding to tumor-associated antigens (TAAs) as well as immune effector cells, thus promoting an immune response against cancer cells. Prostate cancer is rich in tumor associated antigens such as, but not limited to, PSMA, PSCA, hK2, and STEAP1 and there is strong biologic rationale for employment of T-cell redirecting BiTEs within the prostate cancer disease space. Early generation BiTE constructs employed in clinical study have demonstrated meaningful antitumor …

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …

Common Variation In A Long Non-Coding Rna Gene Modulates Variation Of Circulating Tgf-Β2 Levels In Metastatic Colorectal Cancer Patients (Alliance), Julia Quintanilha, Alexander Sibley, Yingmiao Liu, Donna Niedzwiecki, Susan Halabi, Layne Rogers, Bert O'Neil, Hedy Kindler, William Kelly, Alan Venook, Howard Mcleod, Mark Ratain, Andrew Nixon, Federico Innocenti, Kouros Owzar

Department of Medical Oncology Faculty Papers

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous …

Keratin 17 Modulates The Immune Topography Of Pancreatic Cancer, Lyanne Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Bai, Emanuel Petricoin, Lynn Matrisian, Edik Matthew Blais, Natalia Marchenko, Felicia Allard, Wei Jiang, Brent Larson, Andrew Hendifar, Chao Chen, Shahira Abousamra, Dimitris Samaras, Tahsin Kurc, Joel Saltz, Luisa Escobar-Hoyos, Kenneth Shroyer

Kimmel Cancer Center Faculty Papers

BACKGROUND: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of …

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …

Complete Pathologic Response To Gemcitabine And Oxaliplatin Chemotherapy After Prior Therapies In A Patient With Hepatocellular Carcinoma And Peritoneal Metastases Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy, Amry Majeed, Sneha Alaparthi, Dina Halegoua-De Marzio, Jaime Eberle-Singh, Wei Jiang, Pramila Rani Anne, Ashesh P. Shah, Wilbur B. Bowne, Daniel Lin

Jefferson Hospital Staff Papers and Presentations

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary …

Oncology Treatment Plan Updates In Epic-Beacon, Rose Dimarco, Pharmd, Bcps, Bcop, Gloria Espinosa, Mat, Pharmd, Bcop, Kelly Miskovsky, Pharmd, Bcop, Gina Hemmert, Pharmd

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Background

In Medical Oncology, the utilization of EPIC-Beacon Treatment Plans is integral for prescribing and administering cancer treatments. These treatment plans typically consist of anticancer infusion medications (chemotherapy, immunotherapy, etc.), supportive care medications, required laboratory orders, and other monitoring recommendations to ensure that patients receive safe and effective care. In 2017, TJUH transitioned from Varian’s Aria to EPIC’s electronic medical record system. Since then, there has not been a formal review of existing plans, and there are many inconsistencies between plans in different cancer types.

Problem Statement:

• Currently, there is not a formal process for review of existing treatment plans, …

Radiomic Biomarkers Of Locoregional Recurrence: Prognostic Insights From Oral Cavity Squamous Cell Carcinoma Preoperative Ct Scans, Xiao Ling, Gregory S. Alexander, Jason Molitoris, Jinhyuk Choi, Lisa Schumaker, Phuoc Tran, Ranee Mehra, Daria Gaykalova, Lei Ren

Department of Radiation Oncology Faculty Papers

INTRODUCTION: This study aimed to identify CT-based imaging biomarkers for locoregional recurrence (LR) in Oral Cavity Squamous Cell Carcinoma (OSCC) patients.

METHODS: Computed tomography scans were collected from 78 patients with OSCC who underwent surgical treatment at a single medical center. We extracted 1,092 radiomic features from gross tumor volume in each patient's pre-treatment CT. Clinical characteristics were also obtained, including race, sex, age, tobacco and alcohol use, tumor staging, and treatment modality. A feature selection algorithm was used to eliminate the most redundant features, followed by a selection of the best subset of the Logistic regression model (LRM). The …

Xpo1 Blockade With Kpt-330 Promotes Apoptosis In Cutaneous T-Cell Lymphoma By Activating The P53-P21 And P27 Pathways, Nitin Chakravarti, Amy Boles, Rachel Burzinski, Paola Sindaco, Colleen Isabelle, Kathleen Mcconnell, Anjali Mishra, Pierluigi Porcu

Kimmel Cancer Center Faculty Papers

Dysregulated nuclear-cytoplasmic trafficking has been shown to play a role in oncogenesis in several types of solid tumors and hematological malignancies. Exportin 1 (XPO1) is responsible for the nuclear export of several proteins and RNA species, mainly tumor suppressors. KPT-330, a small molecule inhibitor of XPO1, is approved for treating relapsed multiple myeloma and diffuse large B-cell lymphoma. Cutaneous T-cell lymphoma (CTCL) is an extranodal non-Hodgkin lymphoma with an adverse prognosis and limited treatment options in advanced stages. The effect of therapeutically targeting XPO1 with KPT-330 in CTCL has not been established. We report that XPO1 expression is upregulated in …

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …

Mcl-1 Mediates Intrinsic Resistance To Raf Inhibitors In Mutant Braf Papillary Thyroid Carcinoma, Maria Cavallo, Jacob Yo, Kayla Gallant, Camille Cunanan, Amirali Amirfallah, Marzieh Daniali, Alyssa Sanders, Andrew Aplin, Edmund Pribitkin, Edward Hartsough

Kimmel Cancer Center Faculty Papers

Papillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAF^V600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response …

Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC₅₀ that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …

Real World Clinical Experience Using Daily Intelligence-Assisted Online Adaptive Radiotherapy For Head And Neck Cancer, Philip Blumenfeld, Eduard Arbit, Robert Den, Ayman Salhab, Tal Falick Michaeli, Marc Wygoda, Yair Hillman, Raphael Pfeffer, Marcel Fang, Yael Misrati, Noam Weizman, Jon Feldman, Aron Popovtzer

Department of Radiation Oncology Faculty Papers

No abstract provided.

Novel Frameless Linac Radiosurgery Solution For Uveal Melanoma, Louis Cappelli, Mehak Khan, Sudheshna Vemula, Christina Hum, Haisong Lui, Yan Yu, Yingxuan Chen, Yechi Zhang, Muhammad Sharif, Wenyin Shi

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Radiation treatment has replaced enucleation as an organ-preservation treatment for patients with uveal melanoma (UM). We developed a novel non-invasive, frameless LINAC based solution for fractionated stereotactic radiosurgery (fSRS) treatment.

METHODS: We designed and constructed the a stereotactic ocular localization box that can be attached and indexed to a stereotactic LINAC tabletop. It contains adjustable LED lights as a gaze focus point and CCD camera for monitoring of the patient's eye position. The device also has 6 infrared spheres compatible with the ExacTRAC IGRT system. Treatment plans were developed using iPLAN Dose version 4.5, with conformal dynamic arcs and …

Risk Of Secondary Malignancies After Pelvic Radiation: A Population-Based Analysis, Connor Mcpartland, Andrew Salib, Joshua Banks, James R. Mark, Costas D. Lallas, Edouard J. Trabulsi, Leonard G. Gomella, Hannan Goldberg, Benjamin Leiby, Robert Den, Thenappan Chandrasekar

Department of Urology Faculty Papers

Background and objective

Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies.

Methods

A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation.

Key findings and limitations

A total of …

Temporal Considerations In Brain Metastases Radiation Therapy: The Intersection Of Chronobiology And Patient Profiles, Nicolas Nelson, Sara Burke, Louis Cappelli, Lauren Matlack, Alexandria Smith, Noelle Francois, Joseph Lombardo, Yash Shah, Kuang-Yi Wen, Ayesha A Shafi, Nicole Simone

Department of Radiation Oncology Faculty Papers

The circadian system, a vital temporal regulator influencing physiological processes, has implications for cancer development and treatment response. Our study assessed circadian timing’s impact on whole-brain radiotherapy outcomes in brain metastases for personalized cancer therapy insights. The aim of the study was to evaluate circadian influence on radiation treatment timing and its correlation with clinical outcomes and to identify patient populations benefiting from interventions synchronizing circadian rhythms, considering subgroup differences and potential disparities. An IRB-approved retrospective analysis of 237 patients undergoing whole-brain radiotherapy for brain metastases (2017–2021), receiving over 80% of treatments in the morning or afternoon, was performed. Survival …

Health Care Costs Among Patients With Hematologic Malignancies Receiving Allogeneic Transplants: A Us Payer Perspective, Richard Maziarz, Usama Gergis, Marie Louise Edwards, Yan Song, Qing Liu, Annika Anderson, James Signorovitch, Rocio Manghani, Ronit Simantov, Heayoung Shin, Smitha Sivaraman

Department of Medical Oncology Faculty Papers

Patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant (allo-HCT) require extensive care. Using the Merative MarketScan Commercial Claims and Encounters database (2016 Q1-2020 Q2), we quantified the costs of care and assessed real-world complication rates among commercially insured US patients diagnosed with a hematologic malignancy and aged between 12 and 64 years undergoing inpatient allo-HCT. Health care resource use and costs were assessed from 100 days before HCT to 100 days after HCT. Primary hospitalization was defined as the time from HCT until first discharge date. Incidence of complications was assessed using medical billing codes from HCT date to …

Isoform Alterations In The Ubiquitination Machinery Impacting Gastrointestinal Malignancies, Srimathi Kasturirangan, Derek Nancarrow, Ayush Shah, Kiran Lagisetty, Theodore Lawrence, David Beer, Dipankar Ray

Department of Medicine Faculty Papers

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we …

Biological Insights From Plasma Proteomics Of Non-Small Cell Lung Cancer Patients Treated With Immunotherapy, Jair Bar, Raya Leibowitz, Niels Reinmuth, Astrid Ammendola, Eyal Jacob, Mor Moskovitz, Adva Levy-Barda, Michal Lotem, Rivka Katsenelson, Abed Agbarya, Mahmoud Abu-Amna, Maya Gottfried, Tatiana Harkovsky, Ido Wolf, Ella Tepper, Gil Loewenthal, Ben Yellin, Yehuda Brody, Nili Dahan, Maya Yanko, Coren Lahav, Michal Harel, Shani Raveh Shoval, Yehonatan Elon, Itamar Sela, Adam Dicker, Yuval Shaked

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.

METHODS: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using …

Integrating Primary Care, Shared Decision Making, And Community Engagement To Facilitate Equitable Access To Multi-Cancer Early Detection Clinical Trials, Cheryl L. Thompson, Adam H. Buchanan, Ronald E. Myers, David S. Weinberg

Department of Medical Oncology Faculty Papers

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many …

Social Needs Risk And Patient Outcomes With Supportive Oncology Care, Rebecca Cammy, Lcsw, Joshua Banks, Ma

Department of Medical Oncology Posters

Objective

This study utilized social risk data in the electronic heath record collected in routine clinical practice and examined relationships with supportive oncology care contacts and patient outcomes.

Prognostic Properties Of Kras Gene Mutation Subtypes In Resected Pancreatic Cancer, Faria Nusrat, Eliyahu Gorgov, Md, Wilbur Bowne, Md, Obehioye Isesele, Akshay Khanna, Harish Lavu, Md, Aditi Jain, Phd, Charles J. Yeo, Md, Avinoam Nevler, Md

Alpha Omega Alpha Research Symposium Posters

Introduction

• Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and therapy-resistant cancer with an overall 5-year survival rate of almost 12%, making it among the most lethal of all major cancers.¹
• PDAC has a distinct genomic profile, with somatic KRAS protooncogene mutations in ~90% of cases.^2,3
• Current literature has not reached a consensus on disease prognosis based on KRAS mutation subtype.^2-5

Therapeutic Antibodies For The Prevention And Treatment Of Cancer, Mukesh Kumar, Akansha Jalota, Sushil Kumar Sahu, Shabirul Haque

Department of Medical Oncology Faculty Papers

The developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against …

Chlormethine Gel In Combination With Other Therapies For Treatment Of Mycosis Fungoides: A Review With Patient Cases, Marco Ardigò, Neda Nikbakht, Miriam Teoli, Laura Gleason, Liliana Crisan, Christiane Querfeld

Department of Dermatology and Cutaneous Biology Faculty Papers

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients …

Correlation Between Melphalan Chemotherapy With Longitudinal Global Strain Indices Of The Left Ventricle In Multiple Myeloma Patients: A Velocity Vector Imaging (Vvi) Echocardiography Study, Liaosadat Mirsafaee, Mohammad Dehghani Firouzabadi, Sayeh Parkhideh, Hassan Vahidnezhad, Fatemeh Dehghani Firouzabadi, Maryam Arab, David M. Yousem, Mersedeh Karvandi

Jefferson Institute of Molecular Medicine Papers and Presentations

Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells, leading to the production of monoclonal immunoglobulins. High-dose chemotherapy with autologous stem cell transplant has been used in the treatment of patients with MM (1). Melphalan (L-phenylalanine nitrogen mustard) is one of the most effective chemotherapeutic drugs in the treatment of MM (2). The side effects of melphalan include anemia, nausea, vomiting, allergic reactions, oral ulcers, nephrotoxicity, and arrhythmia at high doses (3). The effect of this drug on cardiac mechanics and heart damage is not well established, as previous studies have only focused on the electrocardiographic and …

Addressing Burden In Caregivers Of Older Adults With Cancer, Lora Rhodes, Lcsw, Kristine Swartz, Md, Caroline Glavin, Lsw, Charlotte Zuber, Kuang-Yi Wen, Phd

Department of Medical Oncology Posters

Background

Forty-two million adults in the United States are providing unpaid care for a family member or friend over the age of 50. For approximately 2.5 million of these caregivers, cancer is the primary illness or disability of their care recipient (National Alliance for Caregiving and AARP, 2020). As baby boomers continue to age, and the number of cancer survivors continues to increase, the need for informal caregivers will expand exponentially.

While Comprehensive Geriatric Assessment (CGA) is recommended for older patients with cancer and distress screening is recommended for all cancer patients, there are currently no recommendations regarding screening for …

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …

Stereotactic Mr-Guided On-Table Adaptive Radiation Therapy (Smart) For Borderline Resectable And Locally Advanced Pancreatic Cancer: A Multi-Center, Open-Label Phase 2 Study, Michael Chuong, Percy Lee, Daniel Low, Joshua Kim, Kathryn Mittauer, Michael Bassetti, Carri Glide-Hurst, Ann Raldow, Yingli Yang, Lorraine Portelance, Kyle Padgett, Bassem Zaki, Rongxiao Zhang, Hyun Kim, Lauren Henke, Alex Price, Joseph Mancias, Christopher Williams, John Ng, Ryan Pennell, M Raphael Pfeffer, Daphne Levin, Adam Mueller, Karen Mooney, Patrick Kelly, Amish Shah, Luca Boldrini, Lorenzo Placidi, Martin Fuss, Parag Jitendra Parikh

Department of Radiation Oncology Faculty Papers

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 …